Yu Yan Xia, Wang Yi, Liu Hong
Cancer Treatment Research Center, Qilu Hospital of Shandong UniversityNo. 107, Wenhua West Road, Jinan, China.
Am J Transl Res. 2017 Jul 15;9(7):3304-3314. eCollection 2017.
Studies have demonstrated that the abnormal expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is associated with multiple malignancies, but its functional role in non-small-cell lung carcinoma (NSCLC) metastasis remains to be elucidated. In the present study, we investigated the role of PTEN in regulating proliferation, migration, and invasion of NSCLC cells by establishing NSCLC cell strains with constitutively silenced or elevated PTEN expression. We demonstrated that ectopic expression of PTEN inhibits migration and invasion of NSCLC cells in vitro through wound healing and Transwell invasion assays. Furthermore, PTEN overexpression in NSCLC cells greatly inhibits cell viability and colony formation, which was confirmed by MTT and colony formation assays. Conversely, further analysis indicated that suppression of PTEN expression via shRNA promotes metastasis and growth of NSCLC cells. Finally, our findings demonstrate that PTEN promotes invasion and migration of NSCLC cells through the integrin αVβ6 signaling pathway. Overall, this study provides novel insights into the role of PTEN as a crucial regulator of NSCLC cell metastasis, and suggests that targeted treatment of PTEN-expressing tumors serves as a new therapeutic target for NSCLC.
研究表明，10号染色体缺失的磷酸酶及张力蛋白同源物（PTEN）的异常表达与多种恶性肿瘤相关，但其在非小细胞肺癌（NSCLC）转移中的功能作用仍有待阐明。在本研究中，我们通过建立PTEN表达持续沉默或升高的NSCLC细胞株，研究了PTEN在调节NSCLC细胞增殖、迁移和侵袭中的作用。我们通过伤口愈合和Transwell侵袭实验证明，PTEN的异位表达在体外抑制NSCLC细胞的迁移和侵袭。此外，NSCLC细胞中PTEN的过表达极大地抑制了细胞活力和集落形成，MTT和集落形成实验证实了这一点。相反，进一步分析表明，通过shRNA抑制PTEN表达可促进NSCLC细胞的转移和生长。最后，我们的研究结果表明，PTEN通过整合素αVβ6信号通路促进NSCLC细胞的侵袭和迁移。总体而言，本研究为PTEN作为NSCLC细胞转移关键调节因子的作用提供了新的见解，并表明针对表达PTEN的肿瘤进行靶向治疗可作为NSCLC的新治疗靶点。
